Marc Esteve

Conservative Treatments of Intraocular Retinoblastoma

OBJECTIVE To describe the efficacy of conservative management of retinoblastoma by an association of conservative ocular therapies and chemothermotherapy. DESIGN Phase II prospective nonrandomized trial. PARTICIPANTS Eighty-three children were included (115 eyes). METHODS Conservative ocular therapies and chemothermotherapy (intravenous carboplatin followed by transpupillary thermotherapy to the tumor) after chemoreduction by 2 cycles of carboplatin and etoposide. MAIN OUTCOME MEASURES Use of external beam therapy and ocular tumor control. RESULTS One hundred fifteen of the 147 affected eyes were eligible for conservative management. Nineteen children had unilateral lesions (22.8%), and 64 (77.1%) had bilateral lesions. Sixty-six children received neoadjuvant chemotherapy before ocular therapy, which consisted of one or a combination of several techniques: chemothermotherapy (65 children [86 eyes]) with a mean of 3 cycles per child, thermotherapy alone (22 children [24 eyes]), cryoapplication (49 children [58 eyes]), and iodine 125 brachytherapy (26 children [29 eyes]). Tumor control was achieved for 97 eyes (84%). At the end of the study, external beam radiotherapy (EBR) was necessary for a total of 9 children (11%) and 13 eyes (12%). Enucleation was necessary for a total of 23 eyes (20%), because of complications in 5 cases. CONCLUSIONS Neoadjuvant chemotherapy with 2 cycles of carboplatin and etoposide followed by ocular therapy and chemothermotherapy achieves satisfactory tumor control and permits a low need for EBR.

Combined Proton Beam Radiotherapy and Transpupillary Thermotherapy for Large Uveal Melanomas: A Randomized Study of 151 Patients

Introduction: Exudation from the tumour scar and glaucoma can be major problems after proton beam irradiation of uveal melanoma and can sometimes lead to secondary enucleation. We conducted a randomized study to determine whether systematic transpupillary thermotherapy (TTT) after proton beam radiotherapy could have a beneficial effect. Patients and Method:Between February 1999 and April 2003, all the patients treated by proton beam radiotherapy for uveal melanomas ≧7 mm thick or ≧15 mm in diameter were included in this study after giving their informed consent. One half of the patients received proton beam radiotherapy alone (60 Gy in 4 fractions) and the other half received the same dose of proton beam radiotherapy followed by TTT at 1, 6 and 12 months. All the information concerning the initial tumour parameters, treatments and follow-up was recorded and a statistical analysis was performed. Results: We randomized 151 patients. The median follow-up was 38 months. The 2 groups of patients were similar in terms of age, gender and tumour characteristics. The patients treated with TTT showed a greater reduction of tumour thickness (p = 0.06), less retinal detachment at the latest follow-up (p = 0.14) and a lower secondary enucleation rate (p = 0.02). Discussion: The present study is the first randomized analysis to demonstrate a significant decrease in the secondary enucleation rate in patients treated with TTT after proton beam radiotherapy. Further studies should be performed to determine whether TTT could be beneficial to smaller tumours and to define its optimal dose.

Wound healing and catheter thrombosis after implantable venous access device placement in 266 breast cancers treated with bevacizumab therapy.

The aim of this study was to determine, in a population with metastatic breast cancer treated with bevacizumab therapy, the incidence of wound dehiscence after placement of an implantable venous access device (VAD) and to study the risk of catheter thrombosis. This study enrolled all VADs placed by 14 anesthetists between 1 January 2007 and 31 December 2009: 273 VADs in patients treated with bevacizumab therapy and 4196 VADs in patients not treated with bevacizumab therapy. In the bevacizumab therapy group, 13 cases of wound dehiscence occurred in 12 patients requiring removal of the VAD (4.76%). All cases of dehiscence occurred when bevacizumab therapy was initiated less than 7 days after VAD placement. Bevacizumab therapy was initiated less than 7 days after VAD placement in 150 cases (13 of 150: 8.6%). The risk of dehiscence was the same from 0 to 7 days. In parallel, the VAD wound dehiscence rate in patients not receiving bevacizumab therapy was eight of 4197 cases (0.19%) (Fisher’s test significant, P<0.001). No risk factors of dehiscence were identified: anesthetists, learning curves, and irradiated patients. VAD thrombosis occurred in four patients (1.5%). In parallel, VAD thrombosis occurred in 51 of 4197 patients (1.2%) not receiving bevacizumab therapy (Fisher’s test not significant; P=0.43). Bevacizumab therapy was permanently discontinued in five patients related to wound dehiscence and in one patient due to extensive skin necrosis. These data suggest the need to observe an interval of at least 7 days between VAD placement and initiation of bevacizumab therapy to avoid the risk of a wound dehiscence requiring chest wall port explant. The risk of VAD thrombosis does not require any particular primary prevention.

Familial retinoblastoma: fundus screening schedule impact and guideline proposal. A retrospective study

AimsTo assess if systematic fundus screening according to an ‘intensive’ schedule alters ocular outcome and to propose fundus screening schedule guidelines for children related to a retinoblastoma patient.MethodsFor children with a positive family history of retinoblastoma, we perform fundus exams shortly after birth under general anaesthesia and then at regular intervals according to schedules based on the risk. Familial retinoblastoma cases seen at our institution from January 1995 to December 2004 were retrospectively classified as ‘screened’ or ‘non-screened’ (NS) and, among the ‘screened’ patients, as ‘intensively screened’ (IS) if screening matched our recommendations or ‘non-intensively screened’ (S). Groups were compared by Fisher exact test for categorical variables and Kruskal–Wallis test for continuous variables.ResultsAmong the 547 retinoblastoma patients managed at our institution during this period, 59 were familial cases. In all, 20 were in the NS group, 23 in the S group, and 16 in the IS group. The number of children enucleated was, respectively, 13, 2, and 0 (P<10−4); external beam radiation (EBRT) was required for, respectively, 6, 0, and 2 children (P<0.009). Chemotherapy burden and visual acuity were not significantly different between groups.ConclusionAn ‘intensive’ fundus screening schedule decreased the need for enucleation and EBRT. Therefore, despite the heavy burden of the screening schedule, we recommend physicians and health-care professionals to better inform and refer children with a family history of retinoblastoma for genetic counselling and proper fundus screening in specialized centres.

Positive effect of regional analgesia (RA) in terminal stage paediatric chondrosarcoma: a case report and the review of the literature.

A 10-year-old girl was treated for progressive left pelvic chondrosarcoma and severe local pain radiating to the ipsilateral lower extremity. Despite high doses of opioids, pain was poorly controlled and treatment resulted in urine retention and constipation. Positive effect on pain (143 out of 181 days) was obtained by regional analgesia. Continuous lumbar epidural opioid infusion led to pain relief and disappearance of symptoms. Port-catheter dysfunction necessitated a change of epidural catheter and the patient was treated that with morphine, bupivacaine and clonidine plus clonazepam which resulted in relief of constipation and restoration of urinary function. The patient subsequently developed an abscess required or subarachoid infusion (morphine associated with clonazepam, clomipramine and corticosteroids). Later bilateral controlateral cordotomy was performed due to absence of analgesia and the patient subsequently died of tumour progression.

Use of a Subcutaneous Implantable Pleural Port in the Management of Recurrent Malignant Pleurisy: Five-Year Experience Based on 168 Subcutaneous Implantable Pleural Ports

INTRODUCTION The authors report their experience in the use of subcutaneous implantable pleural port (SIPP) catheters for the treatment of symptomatic recurrent malignant pleurisy. MATERIALS AND METHODS Single-center, prospective follow-up of 137 patients (168 SIPPs). RESULTS No SIPP placement failures were observed. All but 3 of the 125 evaluable patients obtained complete or partial relief of their dyspnea. Seventy-six patients (60.3%) were receiving chemotherapy. Spontaneous pleurodesis was observed within 2 months in 46 patients (36.8%). Twenty-six patients (20.8%) died during the month following SIPP placement. Forty-one patients (32%) survived for more than 6 months. The overall median survival time was 344 days. Three infectious complications (1 empyema, 2 cellulitis) and 3 mechanical complications were observed. The role of pleurodesis as prognostic factor was assessed. Seventy-one patients survived for more than 2 months, 36 with pleurodesis, 35 without pleurodesis, requiring repeated pleural aspiration. The difference observed between the two groups by the 120th day was no longer significant when chemotherapy was taken into account. CONCLUSION SIPP is a safe and effective option for the outpatient management of recurrent malignant effusions and could be considered as first-line treatment in all patients with bilateral, compressive pleural effusion or poor lung reexpansion.

Prévention par la naloxone des effets secondaires de l'analgésie péridurale par morphine pour douleur cancéreuse

Forty cancer patients were randomly assigned to two groups (n = 20). All had incapacitating pain unresponsive to the usual non opioid analgesic drugs. An epidural catheter was set up at the level of the most painful metamere, and made to pass subcutancously so as to exit either in the supraclacicular fossa, or on the patients flank. At T0, the patients were given 4 mg morphine hydrochloride diluted in 10 ml normal saline. Thirty min later, patients in the naloxone group (group N) were given a 0.4 mg bolus, followed by a constant rate infusion of 5 μg · kg−1 · h−1, of naloxone hydrochloride during 18 h. Patients in group P (placebo) were given normal saline instead. The degree of pain was studied with a visual analogue scale and analgesia was assessed by a clinician on a five point scale. These two parameters were obtained half an hour after the injection of morphine and 2, 4, 6 and 24 hours later. At the same times, the patients were questionned about adverse side-effects : nausea, vomiting, pruritus, dysuria, urinary retention. Respiratory depression was assessed clinically and biologically (blood gas measurements at the afore mentioned times). Heart rate, systolic and diastolic blood pressure were also measured. There was no statistically significant difference between the groups in quality and duration of analgesia. Pain reached its lowest level 4 h after the injection of morphine, returning to half its original value at the 24th h. This was also true for the incidence of nausea (11 in group N, 5 in group P), vomiting (3 in both groups), and urinary retention (6 in group P, 5 in group N). However, 1 case of pruritus occured in the naloxone group, and 4 in the placebo group. There were also two cases of respiratory depression in group P ; in fact, breathing rate was lower in this group than in group N throughout the study, but with no increase in Paco2. Lastly, systolic blood pressure was significantly lower than at T0 in group P (− 5.4 mmHg), and higher in group N (+ 7.6 mmHg). These results might tend to show some beneficial effect of naloxone in the prevention of respiratory depression and pruritus in cancer patients given epidural morphine. However, a larger group of patients, such as that of a multi-center trial, is needed to substantiate them.

Conservative treatment of retinoblastoma: a prospective phase II randomized trial of neoadjuvant chemotherapy followed by local treatments and chemothermotherapy

PurposeIntraocular retinoblastoma treatments often combine chemotherapy and focal treatments. A first prospective protocol of conservative treatments in our institution showed the efficacy of the use of two courses of chemoreduction with etoposide and carboplatin, followed by chemothermotherapy using carboplatin as a single agent and diode laser. In order to decrease the possible long-term toxicity of chemotherapy due to etoposide, a randomized neoadjuvant phase II protocol was conducted using vincristine–carboplatin vs etoposide–carboplatin.Patients and methodsThe study was proposed when initial tumor characteristics did not allow front-line local treatments. Patients included in this phase II noncomparative randomized study of neoadjuvant chemotherapy received vincristin–carboplatin (new arm) vs etoposide–carboplatin (our reference arm). They were subsequently treated by local treatments and chemothermotherapy. Primary end point was the need for secondary enucleation or external beam radiotherapy (EBRT) not exceeding 40% at 2 years.ResultsA total of 65 eyes in 55 children were included in the study (May 2004 to August 2009). Of these, 32 eyes (27 children) were treated in the arm etoposide–carboplatin and 33 eyes (28 children) in the arm vincristin–carboplatin. At 2 years after treatment, 23/33 (69.7%) eyes were treated and salvaged without EBRT or enucleation in the arm vincristin–carboplatin and 26/32 (81.2%) in the arm etoposide–carboplatin.ConclusionEven if the two treatment arms could be considered as sufficiently active according to the study decision rules, neoadjuvant chemotherapy by two cycles of vincristine–carboplatin followed by chemothermotherapy appear to offer less optimal local control than the etoposide–carboplatin combination.

Treatment of retinoblastoma: The Institut Curie experience on a series of 730 patients (1995 to 2009).

INTRODUCTION To describe the results of retinoblastoma treatment from 1995-2009 in a single institution. MATERIAL AND METHODS Retrospective review of the charts of patients treated for retinoblastoma. Clinical characteristics at diagnosis, treatments and outcomes in terms of survival and ocular preservation are described. RESULTS During the study period 826 children were referred for retinoblastoma and 730 were managed in our institution. Four hundred and eleven children presented with unilateral retinoblastoma and 319 with bilateral retinoblastoma. Median follow-up is of 93 months. Global survival is 98.5% of children, 10 children presented with second tumors, 11 children died (6 of tumor-related causes). Of the 411 children with unilateral retinoblastoma enucleation was needed at diagnosis for 324 (78.8%). Conservative treatments were attempted for 87 patients (21.2%) and ocular preservation obtained for 65 patients (74% of eyes). Three hundred and nineteen patients presented with bilateral retinoblastoma. Three hundred and ten could be treated conservatively for at least one eye. Initial intravenous chemotherapy was necessary for 75% of them. Ocular preservation without external beam radiation was possible for 221 patients (70%). The use of EBR decreased significantly after 2004 (9.1% of eyes vs 25.1%: P<0.001). DISCUSSION Management and treatment of retinoblastoma are complex, adapted to the extent of the disease. Survival is good. Enucleation is still required for extensive ocular disease, especially for unilateral patients. Intravenous chemotherapy allows good tumor control and eye preservation and decrease the need of EBR. CONCLUSIONS Retinoblastoma treatment with intravenous chemotherapy and ocular adjuvant therapies is very effective on the local tumor control and eye preservation.

Résultats de l’implant en hydroxyapatite naturelle recouvert de treillis de Vicryl® dans une série de 704 cas d’énucléation

PURPOSE Retrospective study of local tolerability of a natural hydroxyapatite orbital implant wrapped with Vicryl(®) (polyglactin) mesh in patients undergoing enucleation. METHOD Complications were classified into four types according to their management: type 1 if no reoperation was required, type 2 if additional surgery without grafting was required, type 3 if an oral mucosal graft was performed (major dehiscence) and type 4 if the complication required removal of the implant. RESULTS Seven hundred and four patients with a median follow-up of 44 months. Five hundred and three patients were enucleated as a primary procedure and 201 after failure of conservative management. The overall complication rate was 12.07% (85 patients) with 68 type 1 complications, nine type 2 complications, three type 3 complications and five type 4 complications (0.71%). A total of 17 patients (2.42%) required additional surgery. The use of chemotherapy or radiotherapy before or after surgery did not influence the results. In univariate analysis, the tolerability was better in children than in adults. With multivariate analysis, only the diameter of the implant was an independent risk factor for complications (P=0.001). CONCLUSION Use of a Vicryl(®) mesh-wrapped natural hydroxyapatite orbital implant after enucleation is particularly well tolerated including the pediatric population. A compromise should be sought with an implant large enough for good cosmetic results but small enough to avoid complications.